Month: May 2021

Categories : Gender Injury & TraumaTags :

Treating Brain Injuries with Sex-specific Interventions

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New research has identified a sex-specific window of opportunity to treat traumatic brain injuries (TBIs), which scientists are exploiting in a project to create a sex-targeted drug delivery for TBI.

The study, a collaboration of The University of Texas Health Science Center at Houston (UTHealth) and Arizona State University will be used to help design nanoparticle delivery systems targeting both sexes for treatment of TBI.

“Under normal circumstances, most drugs, even when encapsulated within nanoparticles, do not reach the brain at an effective concentration due to the presence of the blood-brain barrier. However, after a TBI this barrier is compromised, allowing us a window of opportunity to deliver those drugs to the brain where they can have a better chance of exerting a therapeutic effect,” said Rachael Sirianni, PhD, associate professor of neurosurgery at McGovern Medical School at UTHealth. Dr Sirianni’s collaborator and co-lead investigator on this grant, Sarah Stabenfeldt, PhD, was the first to demonstrate that the window of opportunity created in the blood-brain barrier differed between men and women, and it was this key finding that led them to apply for funding.

TBI results from blows to the head, and in the most severe form of TBI, the entirety of the brain is affected by a diffuse type of injury and swelling. The body responds with an acute response to the injury, followed by a chronic phase as it tries to heal.

“In this second phase, a variety of abnormal processes create additional injury that go well beyond the original physical damage to the brain,” Dr Sirianni said.

Normally, the blood vessels maintain a very carefully controlled blood-brain barrier to prevent the entry of harmful substances. However, during this second phase of healing following a TBI, those blood vessels are compromised, possibly allowing substances to seep in.

One of the numerous differences between female and male patients is varying levels and cycles of sex hormones such as oestrogen, progesterone, and testosterone. While these levels already differ in healthy people, additional hormone disruption for both sexes can result from a brain injury.

Dr Sirianni explained that this work is extremely important as presently TBIs have no effective treatment options. Current treatments for TBI vary widely based on injury severity and range from daily cognitive therapy sessions to radical surgery such as bilateral decompressive craniectomies. 

“The goal of this research is to develop different nanoparticle delivery systems that can target the unique physiological state of males versus females following a TBI. Through this research, we hope to develop an optimum distribution system for these drugs to be delivered to the brain and can hopefully find an effective treatment plan for TBIs,” Sirianni said.

Drugs that previously perceived as unsafe or ineffective when given systemically can instead be targeted directly to the injury microenvironment through nanoparticle delivery systems.

“With these nanoparticle systems, we’re looking at how we can revisit a drug that showed promise in preclinical studies or clinical trials but then failed,” Stabenfeldt said.

Source: The University of Texas Health Science Center at Houston

Categories : Cardiovascular Disease New Compounds and TreatmentsTags :

Averting Heart Failure by Shutting Down a Heart Protein

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Photo from Olivier Collett on Unsplash
Photo from Olivier Collett on Unsplash

Shutting down a protein found in cardiac muscle could be a new mechanism to treat post-heart attack heart failure, according to research led by the University of Cambridge.

New drugs are needed to improve the heart’s pumping ability after damage from a heart attack. Drugs that strengthen the contraction of failing heart muscle have been deemed unsafe, leaving a gap in the heart attack and heart failure armamentarium.

Researchers now believe that they might have identified a new drug target—a protein called MARK4.

In research funded by the British Heart Foundation (BHF), Cambridge scientists found levels of MARK4 were elevated in mouse hearts after a heart attack. When they compared mice with and without MARK4 in the heart, they found hearts lacking the protein pumped blood 57% more efficiently. This protective effect was seen 24 hours after a heart attack and persisted over the entire follow-up period of four weeks.

The team was first in identifying that MARK4 fine-tunes a structural network within the heart muscle cell—called the microtubule network—that attaches to the machinery governing heart muscle cells contraction and relaxation. When MARK4 levels were increased after a heart attack, microtubules were tightly anchored onto the contractile machinery in the heart, increasing resistance and hindering normal function. When MARK4 levels were reduced, microtubules were loosely anchored, making contraction and relaxation easier.

Following a heart attack the speed of contraction in MARK4-lacking muscle cells increased by 42 percent and the speed of relaxation increased by 47 percent, compared to muscle cells from mice that had the MARK4 protein. They were also almost on par with healthy heart muscle performance, attesting to the power of reducing MARK4.

Based on these findings, the researchers suggested that drugs to switch off MARK4 could be a new way to improve recovery and help the heart to pump blood more efficiently in people with failing hearts.

Dr Xuan Li, BHF Intermediate Research Fellow at University of Cambridge BHF Centre of Research Excellence, said: “After years of research we’ve revealed an entirely new and promising way that could help the recovery of failing hearts.

“It’s early days, and we now need to test the longer-term effects of switching off MARK4. But if drugs to do that prove successful, the life-changing benefits could be seen in people with other types of heart disease as well as those who’ve had a heart attack and developed heart failure.”

Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation, said: “Heart attacks are a major cause of disability worldwide—people who’ve had a major heart attack are at much greater risk of developing chronic heart failure. There are around 920 000 people living with heart failure in the UK, and we desperately need drugs to drastically improve the heart’s function in these patients.

“These findings are a positive step forward. Further research is needed to refine and test drugs that can target MARK4 before we’ll see them given to people who’ve had a heart attack and develop heart failure.”

Source: University of Cambridge

Categories : Cardiovascular Disease Mental HealthTags :

Study Links OCD to Increased Risk of Stroke

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Photo by Annie Spratt on Unsplash

Adults with obsessive-compulsive disorder (OCD) were more than three times as likely to have an ischaemic stroke later in life compared to adults who do not have OCD, according to new research.

OCD involves intrusive thoughts which may be accompanied by actions to alleviate the stress brought on by these thoughts; these are called obsessions and compulsions, respectively. Potentially debilitating, OCD typically manifests in adolescence and is under-reported and under-treated. The World Health Organization ranks OCD as one of the ten most disabling conditions worldwide, with a lifetime prevalence of 1% to 3%.

Clinical research has shown that patients with OCD often have stroke-related metabolic disorders, such as obesity and diabetes. 

While a growing body of evidence suggests an association between OCD and stroke risk, with some patients developing OCD after a stroke, OCD may also influence stroke risk. OCD raises the risk for ischaemic stroke more than 3-fold, especially among older adults
Drawing on health records from 2001-2010 from the Taiwan National Health Insurance Research Database, researchers compared stroke risk between 28 064 adults diagnosed with OCD and 28 064 adults without an OCD diagnosis. The average age at diagnosis was 37 years old, with equal representation of men and women, with a maximum data coverage of 11 years.

Analysis showed that even after controlling for factors known to increase stroke risk such obesity and high blood pressure, OCD remained an independent risk factor for ischaemic stroke. However, no differences were found when considering hemorrhagic strokes, and medications to treat OCD were linked to increased risk of stroke.
Ya-Mei Bai, MD, PhD, Professor, Department of Psychiatry, Taipei Veterans General Hospital, said: “The results of our study should encourage people with OCD to maintain a healthy lifestyle, such as quitting or not smoking, getting regular physical activity and managing a healthy weight to avoid stroke-related risk factors.”

Worldwide, stroke is the second-leading cause of death after heart disease. Cerebrovascular diseases often present complex cases, and this study was the first to consider how OCD and strokes may be associated on a longer time scale. 

Limitations include the observational nature of the study being unable to establish cause and effect, as well as the inclusion in the data of only stroke patients who sought health care. Additionally, information on disease severity and outcome was not included along with family medical history or environmental influences, which can further affect both the extent of OCD and severity of strokes.

“For decades, studies have found a relationship between stroke first and OCD later,” said Prof Bai. “Our findings remind clinicians to closely monitor blood pressure and lipid proles, which are known to be related to stroke in patients with OCD. More research is needed to understand how the mental processes connected to OCD may increase the risk of ischaemic stroke.”

Source: News-Medical.Net

Journal information: Chen, M-H., et al. (2021) Increased Risk of Stroke in Patients With Obsessive-Compulsive Disorder: A Nationwide Longitudinal Study. Stroke: Journal of the American Heart Association. doi.org/10.1161/STROKEAHA.120.032995.

Categories : General Interest Mental HealthTags :

Rough Night? Perhaps Skip the Coffee, Study Suggests

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Photo by Toa Heftiba on Unsplash

Depending on coffee to get through the day after a night of poor sleep isn’t always the answer, suggests a new study from Michigan State University.

Researchers from MSU’s Sleep and Learning Lab, led by psychology associate professor Kimberly Fenn, assessed the effectiveness of caffeine in counteracting the negative effects of sleep deprivation on cognition. It turned out that caffeine only helps up to a point.

The study assessed the impact of caffeine following a night of sleep deprivation. The study recruited over 275 participants who were asked to complete a simple attention task as well as a more challenging ‘placekeeping’ task where tasks had to be completed in a specific order without skipping or repeating steps.

Asst Prof Fenn’s study is the first to investigate the effect of caffeine on placekeeping after a period of sleep deprivation.

“We found that sleep deprivation impaired performance on both types of tasks and that having caffeine helped people successfully achieve the easier task,”  said Asst Prof Fenn. “However, it had little effect on performance on the placekeeping task for most participants.”

She added: “Caffeine may improve the ability to stay awake and attend to a task, but it doesn’t do much to prevent the sort of procedural errors that can cause things like medical mistakes and car accidents.”

The US population has a pervasive lack of sleep, a problem that has intensified during the pandemic, Asst Prof Fenn said. Having inadequated sleep impacts not only cognition and mood, but can eventually weaken immunity.

“Caffeine increases energy, reduces sleepiness and can even improve mood, but it absolutely does not replace a full night of sleep, Fenn said. “Although people may feel as if they can combat sleep deprivation with caffeine, their performance on higher-level tasks will likely still be impaired. This is one of the reasons why sleep deprivation can be so dangerous.”

Asst Prof Fenn said that the study has theoretical and practical implications.

“If we had found that caffeine significantly reduced procedural errors under conditions of sleep deprivation, this would have broad implications for individuals who must perform high stakes procedures with insufficient sleep, like surgeons, pilots and police officers,” she concluded. “Instead, our findings underscore the importance of prioritising sleep.”

The study can be found online.

Source: Michigan State University

Categories : Metabolic DisordersTags :

Familial High Cholesterol Often Eludes Genetic Testing

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Image source: National Cancer Institute/Unsplash

Most familial hypercholesterolemia (FH) cases would go undetected if people were to rely on array-based genetic tests alone, a new study suggests.

FH predisposes people to elevated levels of LDL cholesterol, which can lead to premature coronary artery disease and early death.  

For example, the 23andMe test, which has a limited screen for only 24 known FH variants, would have missed over 60% of individuals with the autosomal dominant disorder. This figure was even worse for non-European ancestry individuals.

“Limited-variant screens may falsely reassure the majority of individuals at risk for FH that they do not carry a disease-causing variant, especially individuals of self-reported Black/African American and Hispanic ancestry,” according to Amy Sturm, of the Geisinger Genomic Medicine Institute in Danville, Pennsylvania, and colleagues.

In their study, limited-variant screening would miss nearly 94% and 85% of Black and Hispanic individuals with confirmed FH pathogenic variants. However this would be true for only a third of Ashkenazi Jewish people.

“The reduced yield of limited-variant screening could result in a major health care disparity for groups already affected by social and medical disenfranchisement that beget serious health disparities including a significantly higher rate of cardiovascular death among Black/African American individuals,” the investigators said.

“When FH is strongly clinical suspected, even if array-based FH reporting has negative results, a clinical genetic test should still be considered,” according to an accompanying note by JAMA Cardiology editors Pradeep Natarajan, MD, MMSc, of Massachusetts General Hospital and Harvard Medical School in Boston, and Elizabeth McNally, MD, PhD, of Northwestern University Feinberg School of Medicine in Chicago.

“Genetic databases overrepresent European ancestry populations and therefore make interpretation of genetic variation more accurate in these cohorts. However, even 64% of the FH mutations in European American individuals would have been missed by the 24-variant [test],” noted Drs Natarajan and McNally.

“Unfortunately, genetic testing for FH is underused, with 90% of affected individuals worldwide remaining undiagnosed and only 3.9% of patients with FH in the U.S. having a record of genetic testing,” noted Dr Sturm and colleagues.

“Recent expert statements recommend that patients suspected of having FH be offered genetic testing and that first-degree relatives of genetically positive individuals be screened for FH by lipid profile or genetic testing,” according to them.

Comprehensive genetic testing with next-generation sequencing (NGS) detects over 2000 potentially pathogenic variants within full genomes. Assay-based screens such as 23andMe only test for a small subset of known variants, and not the number present.

Both types of genetic tests for FH are available either in clinical settings or as a direct service to consumers.

“Whether testing is obtained directly by a consumer or through a clinical setting, those tested should consult with a genetic counselor or other qualified health care professional to fully understand the benefits and limitations of the different types of genetic testing for FH,” Sturm’s group urged.

For the study, the authors took deidentified NGS results, sourced from a single clinical laboratory, for gene panels of individuals receiving comprehensive genetic testing either for an FH indication (4563 participants) or as proactive health screening (6482 participants).

The researchers had tested both cohorts for more than 2000 possible variants in four FH-associated genes: LDLR, APOB, PCSK9, and LDLRAP1.

With the limited screening tests, only 8.4% of people with FH indication had a positive detection, compared to 27.0% for comprehensive NGS genotyping. In the proactive cohort of people with no clinical suspicion of FH, clinically significant FH variant prevalence was about one in 191 according to the comprehensive test.

A limitation was the researchers’ inability to confirm genetic testing results with medical and family histories.

Source: MedPage Today

Journal information: Sturm AC, et al “Limited-variant screening vs comprehensive genetic testing for familial hypercholesterolemia diagnosis” JAMA Cardiol 2021; DOI: 10.1001/jamacardio.2021.1301.

Categories : COVIDTags :

President Biden Orders Deeper Probe into COVID Origins

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Photo by Giacomo Carra on Unsplash


US President Joe Biden has ordered intelligence officials to “redouble” their efforts in investigating the origins of COVID, as well as the theory that it was a ‘lab leak’ in China.

This comes days after details of a US intelligence report emerged in the Wall Street Journal, claiming that three doctors working at the Wuhan Institute of Virology had fallen ill with COVID-like symptoms in November 2019 – about when epidemiologists believe SARS-CoV-2 first began circulating in humans. 

Mr Biden said the US intelligence community was divided on whether it was the result of a lab accident, or from jumping from human to animal. Mr Biden asked the groups to report back to him within 90 days.

China’s embassy in the US made a warning statement posted on its website, without mentioning the president’s remarks. “Smear campaigns and blame shifting are making a comeback, and the conspiracy theory of ‘lab leak’ is resurfacing.
“To politicise origin tracing, a matter of science, will not only make it hard to find the origin of the virus, but give free rein to the ‘political virus’ and seriously hamper international cooperation on the pandemic,” it said.

Authorities linked early COVID cases to a seafood market in Wuhan, leading scientists to theorise the virus first passed to humans from animals.

Why now?

In a White House statement released on Wednesday, President Biden said he had asked for a report on the origins of COVID after taking office, “including whether it emerged from human contact with an infected animal or from a laboratory accident”. He asked for “additional follow-up” on receiving the report.

Mr Biden said most of the intelligence community had “coalesced” around those two scenarios, but “do not believe there is sufficient information to assess one to be more likely than the other”.

The president has now asked agencies to “redouble their efforts to collect and analyse information that could bring us closer to a definitive conclusion”, and report to him within 90 days.

He concluded by saying the US would “keep working with like-minded partners around the world to press China to participate in a full, transparent, evidence-based international investigation and to provide access to all relevant data and evidence”.

Beijing meanwhile has previously suggested a possible US lab origin for COVID. The Chinese embassy said it supported a full investigation into “some secretive bases and biological laboratories all over the world”.

Mr Biden’s statement coincided with a CNN report that the president’s administration earlier this year shut down a state department investigation into a possible lab leak origin.

The ‘lab leak’ theory

When they first arose last year, the laboratory leak allegations were widely dismissed as a fringe conspiracy theory, with many US media outlets describing the claims as debunked or false after then-President Donald Trump said COVID had originated from the Wuhan Institute of Virology.

Two months ago, the World Health Organization (WHO) issued a joint report with Chinese scientists on COVIDs origins, rating the likelihood of an accidental lab release as “extremely unlikely”. However the WHO Director-General Tedros Adhanom Ghebreyesus said that he was not satisfied that the investigation had looked at this possibility enough to rate. The investigation only stirred up more interest in the ‘lab leak’ theory, with 18 scientists signing an open letter calling for more investigation before it could be ruled out.

There is little evidence for the ‘lab leak’ theory in the public domain however, and intelligence reports such as the one the Wall Street Journal based its story on are often of unproven provenance. 

Chief White House medical adviser Anthony Fauci still believes that COVID jumped from animals to humans, though this month he admitted he was no longer confident COVID had developed naturally.
Mounting pressure

Mr Biden’s statement comes the day after Xavier Becerra, US secretary for health and human services, urged the WHO to ensure a “transparent” investigation into the virus’s origins.

“Phase 2 of the Covid origins study must be launched with terms of reference that are transparent, science-based and give international experts the independence to fully assess the source of the virus and the early days of the outbreak,” Mr Becerra said.

On Tuesday, Mr Trump sought to take credit in an emailed statement to the New York Post, saying: “To me it was obvious from the beginning but I was badly criticised, as usual. Now they are all saying: ‘He was right.'”

Source: BBC News

Categories : Medical Research & Technology Skeletal SystemTags :

New Biomaterial Produced from Frog Skin and Fish Scales

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Photo by Robert Zunikoff on Unsplash

Researchers at Nanyang Technological University, Singapore (NTU Singapore) have developed a new biomaterial made entirely from discarded bullfrog skin and fish scales that could help in bone repair.

The porous biomaterial, which contains the same compounds that are predominant in bones, acts as a scaffold for osteoblasts, or bone-forming cells, to adhere to and multiply, leading to new bone formation. Bone-forming cells successfully latched onto the biomaterial and started growing, and it was found to have a low inflammatory risk.

This kind of scaffold could help regenerate bone tissue lost to disease or injury, such as jaw defects from trauma or cancer surgery. It could also assist bone growth around surgical implants such as dental implants.

The current standard practice of using a patient’s own tissues means extra surgery is needed for bone extraction. The biomaterial used, frog skin and fish scales, are a significant waste stream produced by Singapore’s aquaculture industry and using them helps repurpose this waste.

‘Waste-to-resource’

“We took the ‘waste-to-resource’ approach in our study and turned discards into a high-value material with biomedical applications, closing the waste loop in the process,” said Dalton Tay, Assistant Professor, Nanyang Technological University. “Our lab studies showed that the biomaterial we have engineered could be a promising option that helps with bone repair. The potential for this biomaterial is very broad, ranging from repairing bone defects due to injury or ageing, to dental applications for aesthetics. Our research builds on NTU’s body of work in the area of sustainability and is in line with Singapore’s circular economy approach towards a zero-waste nation.”

To make the biomaterial, the team first extracted Type 1 tropocollagen (many molecules of which form collagen fibres) from the discarded skins of the American bullfrog and hydroxyapatite (a calcium-phosphate compound) from the scales of snakehead fish, commonly known as the Toman fish.

Collagen and hydroxyapatite (HA) are two predominant components found in bones, thus conferring on the biomaterial a structure, composition, and ability to promote cell attachment similar to bone, as well as toughness.

The scientists removed all impurities from the bullfrog skin, then blended it to form a thick collagenous paste that is diluted with water, from which collagen was extracted. “Using this approach, we were able to obtain the highest ever reported yield of collagen of approximately 70 per cent from frog skin, thus making this approach commercially viable,” said Asst Prof Tay, who is also from the NTU School of Biological Sciences (SBS).

HA was harvested from discarded fish scales through calcination – a purification process that requires high heat – to remove the organic matter, and then air-dried.

The biomaterial was synthesised by adding HA powder to the extracted collagen, then cast into a mould to make a 3D porous scaffold — a two-week process which the team believes can be shortened.

Testing the biomaterial

To assess the biological performance of the porous biomaterial scaffold for bone repair, the scientists seeded bone-forming cells onto the scaffold.

The cells proliferated, and after a week, the cells were uniformly distributed across the scaffold – an indicator that the scaffold could promote proper cellular activities and eventually lead to tissue formation. The scientists also found that the presence of HA in the biomaterial significantly enhanced bone formation.

The biomaterial was also tested for its tendency to cause an inflammatory response, which is common after a biomaterial is implanted in the body.

Using real-time polymerase chain reaction, the scientists found that the expression of pro-inflammatory genes in human immune cells exposed to the biomaterial stayed “relatively modest” compared to a control exposed to endotoxins, a compound known to stimulate immune response, said Asst Prof Tay.

For instance, the expression of the gene IL6 in the biomaterial group was negligible and at least 50 times lower than that of the endotoxins-exposed immune cells. This suggests that the risk of the NTU-developed biomaterial to trigger an excessive acute inflammatory response is low.

The team is now further evaluating the long-term safety and efficacy of the biomaterial as dental products. Further research would involve studying how the body responds to this biomaterial in the long term, as well its use in other applications such as skin wounds, along with further development of the waste-to-resource pipeline.

A preprint copy of the article is available as a PDF for download.

Source: Nanyang Technical University

Categories : COVID General InterestTags :

COVID Sniffer Dogs Have a 94% Sensitivity, Study Shows

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Image by Foto-Rabe from Pixabay

Quickly and efficiently screening incoming travellers for COVID is currently beyond present technology, but dogs — with their keen sense of smell that has aided humans for thousands of years — may be a solution.

An Ekurhuleni-based company is in the final stages of training dogs to be deployed as COVID sniffers at South African points of entry, just in time for the expected third wave, eNCA reports.

Currently, the most widespread test is the rapid antigen (lateral flow) test, which has been shown to produce more false positives for COVID than real detections in low prevalence situations — such as travellers arriving in a country.

Alternatively, the polymerase chain reaction (PCR) test has the greatest sensitivity but is time-consuming and expensive. And most currently available tests involve nasopharyngeal swabs — an unpleasant experience for most people. 

Dogs, with their keen sense of smell have long been used to sniff out drugs and explosives. In recent years they have also been trained to sniff out certain cancers and malaria, although they are not regularly used for this.
Using medical sniffer dogs has the advantage of being extremely quick and could be used in resource-constrained settings.

In the first months of the pandemic, many wondered whether dogs could in fact smell the disease, and began training dogs to see if it was possible. 
Past studies had already established that the volatile organic compounds (VOCs) released in body odour change during respiratory infections. VOCs associated with COVID infection showed a clear distinction between infected and uninfected individuals, suggestive of a strong, distinctive smell.

Initial trials with trained sniffer dogs at airports in France, Lebanon and FInland found that the dogs were even capable of detecting infection before it could be picked up with clinical tests.

A recent study led by the London School of Hygiene & Tropical Medicine (LSHTM) estimated that a plane with 300 passengers could be screened in 30 minutes with two sniffer dogs, and only those passengers identified by the dogs would be required to take a PCR test.

The study, which is not yet peer-reviewed and which is currently available as a pre-print, found that dogs could be trained to detect COVID in 94.3% (test sensitivity) — comparable to the gold standard of PCR tests with 97.2% sensitivity. They also have a specificity of 92%, meaning that they have a low rate of false positives.

Dr Claire Guest, Chief Scientific Officer at Medical Detection Dogs, which assisted in the study, said: “These fantastic results are further evidence that dogs are one of the most reliable biosensors for detecting the odour of human disease. Our robust study shows the huge potential for dogs to help in the fight against COVID.

“Knowing that we can harness the amazing power of a dog’s nose to detect COVID quickly and non-invasively gives us hope for a return to a more normal way of life through safer travel and access to public places, so that we can again socialise with family and friends.”

Besides simple detection, the dogs could also serve as a visible deterrent to people wanting to travel with fake COVID passports, the authors said.
The findings of their study also provided valuable knowledge which could be applied to future pandemics.
The authors acknowledged the limitation that the dogs were conducting the tests in a controlled environment as opposed to the real world.

Primary source: London School of Hygiene & Tropical Medicine

Secondary source: eNCA

Journal information: Pre-print available online

Categories : Cardiovascular DiseaseTags :

Unexpected Discovery Opens Up Stroke and Cardiac Arrest Treatments

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Image source: Pixabay

In a surprising discovery, researchers at Massachusetts General Hospital (MGH) identified a mechanism that protects the brain from the effects of hypoxia. This serendipitous finding, which they report in Nature Communications, could help develop therapies for strokes, as well as brain injury resulting from cardiac arrest.

However, this study began with a very different objective, explained senior author Fumito Ichinose, MD, PhD, an attending physician in the Department of Anesthesia, Critical Care and Pain Medicine at MGH, and principal investigator in the Anesthesia Center for Critical Care Research. Ichinose and his team are developing techniques for inducing suspended animation, a state similar to hibernation where a human’s body functions are temporarily slowed or halted for later revival. 

Ichinose believes that the ability to safely induce suspended animation could have valuable medical applications, such as pausing the life processes of a patient with an incurable disease until an effective therapy is found. Often seen in science fiction, and currently studied by NASA, it could also allow humans to travel long distances in space.

A 2005 study found that inhaling a gas called hydrogen sulfide caused mice to enter a state of suspended animation. Hydrogen sulfide, which smells like rotten eggs, is sometimes called ‘sewer gas.’ Oxygen deprivation in a mammal’s brain leads to increased production of hydrogen sulfide. As this gas accumulates in the tissue, hydrogen sulfide can halt energy metabolism in neurons, causing them to die. Oxygen deprivation is a hallmark of ischaemic stroke, the most common type of stroke, and other injuries to the brain.

At first, Dr Ichinose and his team set out to study the effects of exposing mice to hydrogen sulfide repeatedly, over an extended period. At first, the mice entered a suspended-animation-like state—their body temperatures dropped and they were immobile. “But, to our surprise, the mice very quickly became tolerant to the effects of inhaling hydrogen sulfide,” said Dr Ichinose. “By the fifth day, they acted normally and were no longer affected by hydrogen sulfide.”

Interestingly, the mice that became tolerant to hydrogen sulfide were also able to tolerate severe hypoxia. Ichinose’s group suspected that enzymes in the brain that metabolise sulfide might be responsible for this. They discovered that levels of one particular enzyme, called sulfide:quinone oxidoreductase (SQOR), rose in the brains of mice when they breathed hydrogen sulfide for several days. They thus hypothesised that SQOR plays a role in resistance to hypoxia.

Nature has strong evidence for this; for example, female mammals resist hypoxia better than males—and the former have higher levels of SQOR. When SQOR levels are artificially reduced in females, their hypoxia resistance drops. (Oestrogen may be responsible for the observed increase in SQOR, as the hypoxia protection is lost when a female mammal’s estrogen-producing ovaries are removed.) Additionally, some hibernating animals, such as the thirteen-lined ground squirrel, are highly tolerant of hypoxia, which allows them to survive as their bodies’ metabolism slows down during the winter. The brain of a typical ground squirrel has 100 times more SQOR than that of a similar-sized rat. However, when the researchers ‘switched off’ expression of SQOR in the squirrels’ brains, they lost their protection against the effects of hypoxia.

Meanwhile, when the researchers artificially increased SQOR levels in the brains of mice, “they developed a robust defense against hypoxia,” explained Dr Ichinose. His team increased the level of SQOR using gene therapy, currently a technically complex, impractical approach. On the other hand, the team demonstrated that ‘scavenging’ sulfide, using an experimental drug called SS-20, reduced levels of the gas, thereby sparing the brains of mice when hypoxic.

Human brains have very low levels of SQOR, meaning that even a modest accumulation of hydrogen sulfide can be harmful, said Dr Ichinose. “We hope that someday we’ll have drugs that could work like SQOR in the body,” he says, noting that his lab is studying SS-20 and several other candidates. Such medications could be used to treat ischemic strokes, as well as patients who have suffered cardiac arrest, which can lead to hypoxia. Dr Ichinose’s lab is also investigating how hydrogen sulfide affects other parts of the body. For example, hydrogen sulfide is known to accumulate in other conditions, such as certain types of Leigh syndrome, a rare but severe neurological disorder usually leading to early death. “For some patients,” said Dr Ichinose, “treatment with a sulfide scavenger might be lifesaving.”

Source: Medical Xpress

Journal information: Eizo Marutani et al, Sulfide catabolism ameliorates hypoxic brain injury, Nature Communications (2021). DOI: 10.1038/s41467-021-23363-x

Categories : Cardiovascular DiseaseTags :

Number and Birth Order of Siblings Affect Risk of Cardiovascular Events

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Photo by Wayne Lee-Sing on Unsplash
Photo by Wayne Lee-Sing on Unsplash

According to a large population study in Sweden, first-born children have a lower risk of cardiovascular events than brothers and sisters born later, but people who are part of a large family with many siblings have an increased risk of these events. The findings were published in the online journal BMJ Open.

While the influence of family history – that is, the health of parents and grandparents – on a person’s health, including cardiovascular risk, is well known, there is now growing interest in how the make-up of a person’s immediate family influences health.

For their large population study, the authors drew on data on 1.36 million men and 1.32 million women born between 1932 and 1960 and aged 30–58 years in 1990 from the Multiple-Generation Register in Sweden. They retrieved data from national registers on fatal and non-fatal cardiovascular and coronary events over the next 25 years.

Analysis of the data showed that first-borns had a lower risk of non-fatal cardiovascular and coronary events than siblings born later. First-born men had a higher risk of death than second and third-born siblings, while first-born women had a higher risk of death than second-born siblings, but equal to further siblings.

Looking at family size, compared with men with no siblings, men with one or two siblings had a lower risk of cardiovascular events, while those with four or more siblings had a higher risk.

Similarly, compared with men with no siblings, men with more than one sibling had a reduced risk of death, whereas those that had three or more siblings had an increased risk of coronary events.

A similar pattern was seen in women. Compared with those without siblings, women with three or more siblings had an increased risk of cardiovascular events, while those with two or more siblings had an increased risk of coronary events. Women with one or more siblings had a lower risk of death.

Since this was an observational study, it cannot establish cause. The authors also noted  some limitations, including that the Swedish registers included no information on diagnostic procedures and there no data were available concerning lifestyle factors, such as body mass index, smoking and diet.

The researchers took into account socioeconomic status, obesity, diabetes, chronic lung disease (COPD) and alcoholism and related liver disorders. They also note that some of their findings conflict with those from previous studies.

The researchers noted that, given the wide variation among countries of policies to support families and the number of children, their findings could have implications for public health.

“More research is needed to understand the links between sibling number and rank with health outcomes,” they say. “Future research should be directed to find biological or social mechanisms linking the status of being first born to lower risk of cardiovascular disease, as indicated by our observational findings.”

Source: BMJ Open

Journal information: Sibling rank and sibling number in relation to cardiovascular disease and mortality risk: a nationwide cohort study, BMJ Open (2021). DOI: 10.1136/bmjopen-2020-042881